IV PCA With or Without Continuous Dose vs Oral Opioid to Maintain Analgesia for Severe Cancer Pain After Successful Titration

Intravenous (IV) Patient Controlled Analgesia (PCA) With or Without Continuous Dose vs Oral Opioid to Maintain Analgesia for Severe Cancer Pain After Successful Hydromorphone Titration: a Multi-center, Phase Ⅲ ，Randomized Trial

Based on the previous HMORCT09-2, the results show that IV PCA for analgesia maintenance improvements control of severe cancer pain after successful titration. Therefore, a study is planned to further explore the difference of efficacy and safety between PCA with continuous + bolus dose versus bolus-only.

Study Overview

• Status: Completed
• Conditions: Cancer Pain
• Intervention / Treatment: Drug: Hydromorphone Hydrochloride Injection; Drug: Hydromorphone Hydrochloride Injection; Drug: Morphine Sulfate Sustained-release Tablets

• Study Type: Interventional
• Enrollment (Actual): 1372
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • China, Fujian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age 18 to 80 years;
2. Histologically or cytologically confirmed malignant solid tumor;
3. Persistent severe cancer-related pain (≥7 at rest on the 11-point numeric rating scale [NRS], where 0=no pain and 10=excruciating pain) in the 24 hours before screening;
4. No radiotherapy to the painful area prior to randomization;
5. No radiotherapy, chemotherapy, hormone therapy, targeted therapy, or bisphosphonate therapy within 7 days before randomization;
6. Successful IPCA-HM titration within the past 24 hours;
7. No history of psychiatric disorders;
8. Ability to complete questionnaires;
9. Ability to correctly understand and follow medication guidance from doctors and nurses;
10. ECOG performance status ≤ 3;
11. Provided written informed consent. Exclusion Criteria

1) Patients with non-cancer-related pain; 2) Patients with paralytic ileus; 3) Patients with brain metastases; 4) Patients with hypersensitivity to morphine or hydromorphone; 5) Abnormal laboratory results: creatinine ≥ 2-fold of upper limit of normal (ULN) value, Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.5-fold of the ULN value (≥ 5-fold for subjects with liver metastasis or primary liver cancer), or Child-Pugh class C liver function; 6) Patients unable to take oral medication; 7) Patients with uncontrolled nausea or vomiting; 8) Prior use of hydromorphone, morphine, or PCA devices within 14 days before screening; 9) Use of monoamine oxidase inhibitor drugs (MAOID) within the two weeks before randomization; 10) Women who are pregnant, lactating, or planning to be pregnant within one month after the trial completion; 11) Patients who abuse alcohol; 12) Patients with any other medical condition or reason, in the investigator's judgment, that would make them unsuitable to participate in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCA with continuous + bolus dose; （1）Intravenous PCA with hydromorphone after successful titration of 24 hours;（2）PCA hydromorphone with continuous infusion where dose/h was the total equianalgesic over the previous 24h divided by 24 and bolus dosage for breakthrough pain was 10%-20% of the total equianalgesic over the previous 24h；lockout time = 10 minutes；（3）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day; (4)The treatment regimen was continued for 7 days.	Drug: Hydromorphone Hydrochloride Injection; Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose (dose/hours) = the total dosage of hydromorphone in the previous 24 hours/24; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours; 3) lockout time = 10 minutes; 4）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.; Drug: Hydromorphone Hydrochloride Injection; Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose = 0; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours: 3) lockout time = 10 minutes; 4)Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.
Experimental: PCA with bolus-only dose; （1）Intravenous PCA with hydromorphone after successful titration of 24 hours; (2)PCA hydromorphone with bolus-only where dosage was 10%-20% of the total equianalgesic over the previous 24h administrated as needed;（3）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day; (4)The treatment regimen was continued for 7 days.	Drug: Hydromorphone Hydrochloride Injection; Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose (dose/hours) = the total dosage of hydromorphone in the previous 24 hours/24; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours; 3) lockout time = 10 minutes; 4）Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.; Drug: Hydromorphone Hydrochloride Injection; Intravenous PCA with hydromorphone after successful titration of 24 hours.the PCA setting: 1) continuous dose = 0; 2) bolus dose = 10-20% of the total dosage of hydromorphone in the previous 24 hours: 3) lockout time = 10 minutes; 4)Evaluate every 24 hours and PCA parameters were adjusted according to the dose of the previous day.
Active Comparator: Oral opioid; （1）Swift to sustained-release morphine orally as background dose with immediate release morphine orally for breakthrough pain after successful titration of 24 hours；(2)Oral sustained-released morphine where total equianalgesic over the previous 24h/2×75% every 12h/day and immediate-release morphine for breakthrough pain was 10%-20% of the total equianalgesic over the previous 24h； (3)Evaluate every 24 hours and the dose for the next day is adjusted according to the dose of the previous day；(4)The treatment regimen was continued for 7 days.	Drug: Morphine Sulfate Sustained-release Tablets; Swift to sustained-release morphine orally as background dose with immediate release morphine orally for breakthrough pain after successful titration of 24 hours. Administration of morphine orally 1) Sustained-release morphine orally (dose/12 hours) = the total equianalgesic of the previous 24 hours/2×75% for day 1; 2）the total equianalgesic of the previous 24 hours/2 for day 2 ; 3）Evaluate every 24 hours and the dose for the next day is adjusted according to the dose of the previous day；4) Immediate release morphine orally = 10-20% of the total equianalgesic of the previous 24 hours;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3DNRS (3-day average Numeric Rating Scale)	The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain. NRS of 24 hours is assessed every day. 3DNRS is a sum of average NRS of Day 1 (D 1) to Day 3 divided by 3 (the day of titration is defined as D0, the first day after titration is defined as D1, the second day after titration is defined as D2, and so on).	up to 4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with an average NRS pain score >3	The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain.	up to 7 days
Number of patients with an average NRS pain score > 6	The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain.	up to 7 days
Daily avNRS score of days 1 to 6	Daily average NRS pain score of days 1 to 6	up to 7 days
Adverse events	assessed by NCI-CTCAE v5.0	up to 8 days
Improvement in physical symptoms and overall well-being	assessed by Chinese version of the Edmonton Symptom Assessment System.	up to 7 days
Patient Satisfaction Score	The satisfaction score of the patients to analgesia was evaluated by 10-point scale: 0 points for dissatisfaction, 10 points for very satisfied, the higher the score, the higher the satisfaction.	up to 7 days
Daily equivalent morphine consumption	Daily equivalent morphine consumption	up to 7 days
Patient Satisfaction Score	from 0 to 10, with 0 = extremely unsatisfied and 10 = extremely satisfied	up to 7 days
Maximum NRS (Days 1 to 6)	Maximum NRS score (Days 1 to 6)	up to 7 days
Daily frequency and duration of breakthrough cancer pain	Daily frequency and duration of breakthrough cancer pain (defined as transient pain exacerbation [NRS ≥4])	up to 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with an average NRS pain score >3	The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain.	up to 7 days
Number of patients with an average NRS pain score > 6	The Numerical Rating Scale (NRS, a score of 0 means no pain and 10 means the most severe) is used to assess the severity of pain.	up to 7 days
Daily opioid dosage	Daily opioid dosage	up to 7 days
Satisfaction score	The satisfaction score of the patients to analgesia was evaluated by 10-point scale: 0 points for dissatisfaction, 10 points for very satisfied, the higher the score, the higher the satisfaction.	up to 7 days
Quality of life of patients	Chinese version of the Edmonton Symptom Assessment System.	up to 7 days
Number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control	The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control	up to 7 days

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital
• Investigators: Principal Investigator: Rong bo Lin, MD, Fujian Cancer Hospital,Department of Gastrointestinal Medical Oncology

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): May 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 18, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Orally; IV PCA with continuous + bolus dose; IV PCA with bolus-only dose
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Morphine; Hydromorphone
• Other Study ID Numbers: SYLT021/HMORCT09-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Anonymized individual participant data and supporting clinical trial documents, including the study protocol, informed consent forms, and statistical analysis plan, will be available upon reasonable request to the corresponding author

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No